Yeast cell factory for mRNA bioproduction

Voices of Leading Scientists on the Occasion of Two Years of Yscript – Dr Urh Černigoj

In April 2022, Yscript embarked on a mission to develop a customised yeast-based messenger RNA factory platform for the large-scale and cost-effective production of mRNA therapeutics. After two years, we now look back together with our leading consortium members on the work done and progress achieved so far.

Read the interview with Dr Urh Černigoj, Head of R&D at Sartorius BIA Separations:

The past two years went by quickly, we are in the second half of the project now and a lot of work has already been conducted. What is the status of the work you are conducting in the project? What would you say is the biggest success/breakthrough that has been achieved so far?

“We have developed and implemented scalable and efficient purification tools for messenger RNA, especially self-amplifying (sa) RNA molecules. saRNA is a very large single-stranded RNA molecule, the purification of which has posed many problems to date. The work done so far was published in established scientific journals, while the industrial relevance of the process is already guaranteed from the point that we are a company producing preparative chromatographic columns for purification of large biomolecules.”

Research projects come with many uncertainties and challenges. What challenges came up in the course of the past two years and how did you manage to overcome them?

“The project started from scratch with many uncertainties and this was going on just after the COVID period. It was not the easiest way in the beginning to establish all the necessary connections. The project goals are also very ambitious and we (Sartorius BIA Separations) as a partner are building our research on the top of previously finished activities of other partners. While waiting for the readiness of the technology to be transferred to our laboratories, we had to find appropriate model systems to work on.”

Looking ahead, what steps are you looking forward to?

“I am looking forward to the point, where all the puzzles will be assembled into one complete story. From the yeast engineering to the purified mRNA molecule. It is still a very ambitious goal.”

A challenging project like Yscript is teamwork. Have there been any personal encounters within or outside the consortium in the last two years that have had a lasting impact on you?

“Of course. We did not know the majority of the partners before the project, because we come from very different scientific/research fields. So we did not know at the beginning, if we would be able to find a common denominator. But now, after two years, I can say, that our diversity enables us to come up with the implementation of ideas, which would be unrealistic, if we were alone. Just now there are extensive discussions and work going on between three partners, where an exploitation of an extremely innovative idea of utilising special oligonucleotides for affinity-based purification of complex RNA samples is taking place.”

Yscript is an EIC pathfinder project – how are your experiences with the programme so far? Do you see any difference to other EU funded projects you are involved in?

“I can hardly answer to this question, because we were not involved in EU projects for almost a decade before successful application to Yscript. It is very difficult to get the EU funding, so in most cases we do not decide for the submission to such projects, as the time required and the obstacles to successful participation are too high.”

Dr Urh Černigoj, Head of R&D at Sartorius BIA Separations